Posted by SalArmy4me on July 10, 2001, at 13:23:30
In reply to Redirected: Advice wanted for newcomer, posted by Dr. Bob on July 10, 2001, at 9:45:34
Psychosomatics
Volume 61(5) September/October 1999 p 712 Dietary Supplements and Natural Products as Psychotherapeutic Agents
Fugh-Berman, Adriane MD; Cott, Jerry M. PhD:John’s Wort (Hypericum perforatum)
SJW is a common roadside plant (Figure 1, A) that has gained much popularity in the United States as an antidepressant (5, 6). Hypericum seems to be an effective antidepressant with an excellent safety profile, but more information is needed on its efficacy compared with SRIs. A MEDLINE search for “St. John’s wort” produced 1547 publications, and a search for “hypericum” produced 141 publications.
Many studies have been performed on this herb in Europe, primarily Germany. A recent meta-analysis evaluated 23 randomized trials (20 were double blind) of SJW in a total of 1757 outpatients with mild to moderate depression (7). Improvement in depressive symptoms (usually measured by the HAM-D or Clinical Global Impression scale) was observed in all groups. In 15 placebo-controlled trials, SJW was found to be significantly more effective than placebo. In eight treatment-controlled trials, clinical improvement in those receiving SJW did not differ significantly from those receiving tricyclic antidepressants.
Most trials were 4 to 8 weeks in duration. The trials in this meta-analysis were heterogenous and used various diagnostic criteria and dosages of herb. In 20 trials, single-herb preparations were tested; the remainder tested combination herb products. Thirteen trials compared a single hypericum preparation with placebo and provided data on treatment responders; of these, 55.1% of those receiving the herb improved, compared with 22.3% of those receiving placebo. No significant differences in treatment effect were found between single-herb preparations of SJW and standard antidepressants. Combination products (containing both hypericum and the sedative herb valerian) also were not significantly different from standard antidepressants. Side effects were reported less often with SJW; 19.8% of those on SJW reported symptoms, compared with 52.8% of those on tricyclic antidepressants.
Diagnostic criteria for depression also differ in Germany, and most of the SJW trials used ICD-9 diagnostic criteria (a few used ICD-10 or DSM-IV criteria). There are no clinical trials comparing SJW to SRIs. In Germany, SRIs became popular only recently; at the time that most SJW studies were performed in Germany, the usual treatment for depression was small doses of tricyclic antidepressants (eg, 75 mg/d imipramine). Whether SJW compares favorably with SRIs in terms of therapeutic benefit and side effects remains to be determined.
One 6-week trial from the United Kingdom (8) using DSM-IV criteria found that the proportion of patients responding to a daily dose of 75 mg of amitriptyline (34 of 78) was similar to those responding to 900 mg of hypericum (37 of 87), but by the end of the study, the total decrease in depression scores favored amitriptyline. Another 6-week trial in 209 more severely depressed patients examined the effects of larger doses of each medication (9). HAM-D scores in those receiving hypericum (1800 mg/d) decreased from 25.3 to 14.4, and in the imipramine (150 mg/d) group, scores decreased from 26.1 to 13.4. Although there was a small advantage for the tricyclic antidepressant over hypericum in both trials, fewer adverse effects were reported with SJW.
The National Institutes of Health National Center for Complementary and Alternative Medicine and National Institute of Mental Health recently contracted with Duke University to conduct a multicenter study comparing SJW with sertraline (Zoloft) and placebo in patients diagnosed with major depression.
Although SJW demonstrates MAO inhibition in vitro, this effect has not been demonstrated in vivo, nor have there been any reported cases of MAO inhibitor–associated hypertensive crises in humans using SJW (7). Although SJW inhibits serotonin, norepinephrine, and dopamine in vitro (10), the concentrations required to attain these effects are quite high and render the chances of attaining equivalent blood concentrations unlikely. The most potent effect of SJW seems to be on GABAA and GABAB receptors, with a median inhibitory concentration of 60 ng/ml for GABAA and 9 ng/ml for GABAB (11). Recent data suggest that a component of the extract called hyperforin may be more important to the therapeutic activity than hypericin (by which it is standardized) (12).
Adverse Effects and Interactions.
Side effects reported for SJW are generally mild. Gastrointestinal symptoms and fatigue have been reported (7). The most predictable effect seems to be photosensitization, especially in fair-skinned people. First noted in light-skinned cows that grazed in pastures in which SJW grew, photosensitization has been demonstrated in a controlled clinical trial involving hypericin and exposure to metered doses of UVA and UVB irradiation (13). Using LI 160, a standardized extract from Lichtwer Pharma (Berlin, Germany), these authors found a measurable increase in erythema in light-sensitive volunteers exposed to UVA irradiation after receiving 600 mg of SJW three times daily for 15 days. This effect has also been seen in humans taking high doses of synthetic hypericin (14). Photosensitization is generally mild and transient, disappearing within a few days of drug discontinuation. Although this effect is usually associated with higher than recommended doses of hypericum, it can occur at lower doses and generally appears on the package labeling as a precaution. No other adverse effects were observed in the high-dose studies.
poster:SalArmy4me
thread:69585
URL: http://www.dr-bob.org/babble/20010708/msgs/69619.html